Ultraviolet (UV) light attracts most flying insects, including human disease vectors such as mosquitoes, flies, and biting gnats; and major agricultural pests. The diseases spread by harmful insects afflict hundreds of millions people worldwide and some insect-mediated diseases such as West Nile virus and dengue fever are alarmingly on the rise in the U.S (note the current epidemic of West Nile disease which is occurring throughout the U.S. and is most severe in Texas). Medical and agricultural damage caused by UV-sensitive insects costs many billions of dollars per year, which has led to the wide use of UV lights for insect control. The currently used versions of light traps are the descendants of designs originating from the Centers for Disease Control in the 1960s. The design of insect control lights is based on the longstanding assumption that UV light detection and behavioral responses are mediated exclusively by UV-sensitive opsins in their eyes and external photoreceptors. Our laboratory has recently identified Cryptochrome (CRY) as another insect UV-sensitive photopigment as a major component for controlling fly behavioral responses to UV light. This exciting new finding followed directly from our recent discovery that blue light photoactivation of insect CRY causes rapid membrane depolarization and up to 300% increased action potential firing rate over baseline dark firing rate in central brain arousal neurons (Sheeb et al., 2007; Fogle et al., 2011). The CRY-mediated electrophysiological light response is robust in the absence of all opsin-based classical photoreceptor inputs (Fogle et al., 2011). Thus it is likely that insect control light technologies could be improved by a better understanding of the physiology of insect UV light response, including taking CRY's properties and physiologically driven processes into account. This proposal provides an innovative plan to explore UV light activation of insect CRYs including a rapid assay to assess the UV sensitivity of CRYs from all known sequences for the most harmful insect disease vectors, including the mosquito species responsible for malaria, dengue fever, yellow fever, West Nile virus and others. Other CRY sequences will become available in the near future for testing the insect vectors for Chagas disease and typhus. We had a solid plan to mechanistically determine the molecular and circuit physiology of how UV light activated CRY determines insect behavioral responses to UV light including aims that if successful will provide clear guidance for improving light devices to attrac and kill greater numbers of harmful insects. These plans include a test whether blue light pre-activation amplifies the biological response of CRY to UV light. Most of our plan centers around the use of LEDs as UV light sources. This was done in consideration for eventual field applications using LEDs for harmful insect control due to recent improvements in LED device longevity, precision of temporal control and power efficiency and low cost. The research plan is supported by very strong preliminary data for all aims and thus has a high probability for producing novel high impact findings.